The Molecular Imaging Branch (MIB) mainly aims to exploit positron emission tomography (PET) as a radiotracer imaging technique for investigating neuropsychiatric disorders, such as depression, schizophrenia and Alzheimer's disease. Fundamental to the mission of the MIB is the development of novel radiotracers that can be used with PET to deliver new and specific information on molecular entities and processes in the living human or animal brain (e.g. regional neuroreceptor concentrations, neurotransmitter synthesis, enzyme concentrations, regional metabolism, amyloid deposition). PET is uniquely powerful for this purpose provided that it can be coupled to appropriate radioactive probes (PET radiotracers). The chemical development of these probes is the key to exploiting the full potential of PET in neuropsychiatric research. The PET Radiopharmaceutical Sciences Section of the MIB is now established to fulfill the need for a concerted effort on PET radiotracer discovery (a process that has some parallels with drug discovery). During this year the first phase of laboratories (~ 4000 sq ft) were commissioned with state-of-the-art facilities for medicinal chemistry and automated radiochemistry with positron-emitting carbon-11 (t1/2 = 20 min) and fluorine-18 (t1/2 = 110 min), radioisotopes that must be produced on a daily basis from the adjacent cyclotrons of the NIH Clinical Center. A scientific program is now established, focusing on developing novel radiotracers for brain receptors or proteins implicated in neuropsychiatric disorders [e.g. cannabinoid (CB-1), serotonin (5-HT1A, 5-HT4, 5-HT7), alpha-1, alpha-2, NET, glutamate (mGluR5), beta-amyloid protein deposits). Initial progress in some of these areas (e.g. NET, 5-HT and glutamate)is already encouraging for eventual successful radioligand development. Candidate radioligands were prepared and found in PET experiments to give detectable receptor-specific signals in animals in vivo. Methodology underpinning these developments was also advanced, in areas such as polymer-supported labeling reactions, microwave-enhanced chemistry and radiochemistry and the development of micro-reactors. new anlytical methods have also been developed. prouctive collaorations have also been established with external academic laboratories and Pharma. The laboratory is already producing some radiotracers for regular PET investigations in animals {e.g. [18F]FECNT (for dopamine transporter imaging), [18F]Fallypride (for dopamine type-2 receptor imaging), [11C]Rolipram (for PDE4 enzyme imaging)} and some of these will also soon be available for brain imagimg in human subjects and clinical research protocols. A second phase of laboratories (2000 sq ft), which will expand the facility for organic synthesis, radiochemistry and biological studies, is planned for 2004/2005.